Inhibition of metformin on acetyl coa carboxylase in human hepatocellular carcinoma cell line HepG2

PENG Xiaoren; LIU Yan; ZOU Dajin

Abstract：Objective To determine the relationship between the antineopastic activity and the regulation on acetyl coa car?boxylase ( ACC) of metformin in human hepatocellular carcinoma cell( HCC) line HepG2. Methods HepG2 cells were treated with various concentrations of metformin(0,1,5,10,15 mmol/L) for 24 h, 48 h and 72 h respectively and cell growth was assessed by CCK?8 assay. After treated with different doses of metformin(0,5,10,15 mmol/L) for 72 h, protein expression levels of AMPKα,P?AMPKα,ACC1,P?ACC were measured by Western blotting method and ACC mRNA expression levels were measured by Real?time PCR. Results The growth of HepG2 cells were inhibited by metformin in dose?dependent and time?dependent manner. After treated with metformin for 72 h, metformin increased AMPK activation and decreased ACC activation respectively as metformin dose levels in?creased. Compared with control group, the protein expression levels of P?AMPKα and P?ACC were both significantly changed in 10mmol/L group and 15 mmol/L group( P<0?01) . ACC mRNA expression levels were decreased significantly in all metformin?treated groups( P<0?01) . Conclusion Metformin inhibits cellular proliferation of HepG2 cell line and suppresses ACC activation in both as?pects of protein phosphorylation and gene expression. Metformin actitiviates AMPK and inhibits ACC, which may implicate with its an?tineopastic activity on HCC.